Although pancreatic islet-cell tumors account for only 1% to 5% of
all pancreatic neoplasms, they represent an important subset of
pancreatic neoplasms due to their substantially improved prognosis
compared to pancreatic adenocarcinoma. (1,2) Pancreatic islet-cell
tumors, also referred to as neuroendocrine tumors, may present with a
broad spectrum of clinical and imaging manifestations, sometimes quite
dramatic, depending on whether lesions are solitary or multiple,
syndromic or nonsyndromic, inherited or sporadic, or benign or
malignant. The role of the radiologist in imaging pancreatic islet-cell
tumors is to localize the tumor and evaluate the extent of disease,
which in turn helps determine whether the patient is an operative
candidate and helps guide therapy.

Ninety-five percent of pancreatic islet-cell tumors are solitary
and sporadic. Generally, these do not exhibit hormonal hypersecretion
(nonsyndromic) and are clinically silent until they grow large enough to
cause symptoms.

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On the other hand, hyperfunctioning islet-cell tumors (referred to
as syndromic islet-cell tumors) manifest much earlier, and at a much
smaller size due to symptoms caused by hormonal oversecretion. Often
these syndromic tumors are barely visible by imaging, in spite of a
dramatic clinical presentation. These tumors are classified according to
the predominant hormone of oversecretion: insulinoma, gastrinoma,
vasoactive intestinal peptide-secreting tumors (VIPoma), glucagonoma,
somatostatinoma, and growth-hormone-releasing factor-secreting tumors
(GRFomas).

Insulinomas account for 50% of all islet-cell tumors and are the
most common islet-cell tumor subtype. (6) The majority of insulinomas
(80% to 90%) are benign, solitary and are <2 cm at presentation. (7)
These tumors cause fluctuations in serum glucose levels in patients,
with associated morbidity related to severe hypoglycemia, occasionally
leading to multiple seizures. Surgical resection of insulinomas is the
treatment of choice, with symptoms promptly resolving after resection.

Pancreatic islet-cell tumors other than insulinomas have a higher
malignancy rate, approaching 60% to 90%. (1) Gastrinomas are the second
most common islet-cell tumor, with approximately 25% associated with
multiple endocrine neoplasia (MEN-1). (4) Resection of gastrinomas is
often difficult due to locally invasive features or metastatic disease
in more than half of patients. (1) When a gastrinoma is suspected, one
should carefully inspect the "gastrinoma triangle," an
anatomic triangle bounded by the junction of the cystic duct insertion
on the common bile duct, the body of the pancreas, and the junction of
the second and third portions of the duodenum (Figure 1). About 85% to
90% of gastrinomas are present within the gastrinoma triangle; the
search for this tumor should not be limited solely to the pancreas but
should include the boundaries of this anatomic triangle. Similarly,
VIPomas, somatostatinomas, and GRFomas may also arise outside of the
pancreas. (4)

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Unlike sporadic islet-cell tumors, inherited pancreatic islet-cell
tumors are usually multiple in location and most often related to MEN-1.
They can also be seen with other syndromes such as Von Hippel-Lindau,
tuberous sclerosis and neurofibromatosis type 1. (3) Whether pancreatic
lesions associated with MEN-1 are more likely benign or malignantis
still much debated. Differentiation between inherited and sporadic
etiologies is important not only because of their different imaging
presentation, but also because they undergo different therapies. (4,5)

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Imaging is helpful in determining extent of disease, with
implications on the patient's overall prognosis. Tumor growth and
spread is considered the major determinant of patient survival.
Pancreatic islet-cell tumors spread first to regional lymph nodes, then
to the liver, bone, and rarely, to distant sites such as the lung or
brain. Lymphovascular invasion is an important feature correlating to
survival. (8) Fifty percent to seventy percent of deaths in patients
with metastatic disease are thought to be caused by tumor progression.
(4)

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Imaging options

Computed tomography (CT) is the initial imaging modality of choice,
but is estimated to detect only 60% to 70% of primary pancreatic
insulinomas and gastrinomas. (9,10) Magnetic resonance imaging (MRI),
intraoperative ulttrasound, endoscopic ultrasound, selective angiography
and portal venous sampling may serve as adjunctive methods of evaluating
disease. (11) Recent literature suggests that MRI may be at least as
sensitive as multiphasic CT in detecting pancreatic islet-cell tumors.
(12) In our experience, a multimodality approach is useful for
diagnosing and staging pancreatic islet-cell tumors as well as helping
to guide surgery (Figures 2-6).

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Treatment

Preoperative imaging evaluation is important for surgical planning
because resection is the only definitive curative treatment, regardless
of benign or malignant pathology. One should determine the location of
the tumor within the pancreas, and assess presence of multiple tumors,
including tumors outside of the pancreas, and looking for evidence of
local invasion or metastatic disease. (13) These findings will affect
surgical candidacy and help guide the type of surgery to be performed,
such as enucleation, partial, or rarely, total pancreatectomy. (14)

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There are several therapeutic options for treating advanced disease
from isletcell tumor. Liver metastases in patients with insulinomas and
gastrinomas are estimated to be present in up to 35% to 74% of cases.
(4) Chemotherapy has been used for metastatic disease with some success
in limited trials. (15) Interferon and octreotide, as well as hepatic
artery embolization or ligation, have also been used. (16,17) In select
cases liver-transplantation has been performed. (14) There is some
controversy over the efficacy of debulking for treatment of metastatic
disease. (15)

The typical appearance of a pancreatic islet-cell tumor is a
well-circumscribed, solitary, hypervascular mass (Figure 4). Because
islet-cell tumors are generally soft, and lack associated desmoplastic
reaction, they do not usually cause pancreatic duct obstruction or
dilation. Mild distortion of the duct may be seen due to adjacent mass
effect or if the tumor is located near the main pancreatic duct(Figure
8).

Typically, pancreatic islet-cell tumors and metastases are best
seen during the late arterial phase (Figures 4, 9). On portal-venous
phase, tumors will characteristically demonstrate late retention of
contrast (Figures 4, 10). While arterial enhancement patterns are
accepted as the most common imaging appearance, atypical enhancement
patterns do occur, and varying opinions on optimal phase of enhancement
have been reported. (9,12,18,19,20) Given the variability in peak
enhancement and enhancement patterns, multiphasic imaging is generally
accepted as the best method to ensure optimal detection of pancreatic
islet-cell tumors.

On ultrasound, pancreatic islet-cell tumors are generally
hypoechoic and well circumscribed. Color Doppler imaging will reveal
prominent vascularity of the tumor. Often the tumor is difficult to
palpate surgically due to its soft texture. Intraoperative ultrasound is
helpful in localizing small tumors and delineating their relationship to
the main pancreatic duct and adjacent vessels (Figure 6).

In patients with inherited islet-cell tumors, multiple
hypervascular pancreatic masses are often present (Figures 11 and 12).
Additionally, other pancreatic lesions are commonly seen, such as
multiple pancreatic cysts in patients with Von Hippel-Lindau syndrome
(Figures 12 and 13).

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Metastatic lesions occurring in the liver are generally
hypervascular in appearance on late arterial-phase scans, with similar
enhancement characteristics as the primary pancreatic neoplasm (Figure
14). Rapid washout from hepatic metastases may render them isodense on
venous-phase acquisitions. It is therefore essential to perform
arterial-phase imaging to detect liver metastases. As with the primary
tumor, liver metastases can become centrally necrotic as they increase
in size (Figure 15). Regional adenopathy, liver, bone and pulmonary
metastases are additional imaging features of advanced disease (Figures
16 and 17).

A commonly cited reason for difficulty in visualizing pancreatic
islet-cell tumors is the presence of adjacent enhancing vessels. Because
pancreatic islet-cell tumors are often intensely vascular, their
appearance in the axial cross-section can either mimic, or be obscured
by, adjacent vessels of similar caliber. (9) Multiplanar reformations as
well as multiphasic imaging can be helpful to avoid this potential
pitfall. Occasionally, hypervascular metastases to the pancreas can
occur, most commonly from renal-cell carcinoma. While rare, these can be
mistaken for a pancreatic islet-cell tumor due to similar enhancement
characteristics. (21)

A typical imaging findings

Atypical imaging appearances of pancreatic islet-cell tumors are
not uncommon. While most islet-cell tumors are well-visualized on CT due
to their hypervascular nature, some may be isoattenuating to the rest of
the pancreas and challenging to visualize. In cases where the lesion is
not immediately apparent, subtle pancreatic duct indentation or subtle
changes in pancreatic duct caliber may be helpful clues in identifying
the location of the lesion (Figure 18). Indeed, small isoattenuating
lesions can be particularly difficult to delineate by CT and in some
cases may be better seen on endoscopic ultrasound or
intraoperativeultrasound.

Another atypical appearance of islet-cell tumors is that of cystic
or necrotic change. Central necrosis is more commonly seen in larger
nonsyndromic pancreatic islet-cell tumors that outgrow their blood
supply. Often the lesion periphery will remain hypervascular while the
center does not enhance (Figures 19 and 20).22 In our experience in one
very rare instance, a pancreatic islet-cell tumor presented with a
purely cystic appearance (Figure 21).

Calcifications are not a typical imaging feature of pancreatic
islet-cell tumors but can be seen in up to 20%, best delineated on CT
(Figures 22 and 23). The presence of calcifications is more suggestive
of a pancreatic islet-cell tumor and can be helpful in differentiating a
lesion from adenocarcinoma of the pancreas. (6)

Vascular encasement, narrowing, and/or frank vascular invasion are
aggressive findings commonly seen in pancreatic adenocarcinoma.
Occasionally, these findings may also be seen with pancreatic islet-cell
tumors. In these atypical islet-cell tumors, the degree of vascular
encasement or occlusion is often disproportionally less than that found
in a similarly sized pancreatic adenocarcinoma (Figures 24-28). Beyond
encasement, direct invasion of the portal vein with resulting tumor
thrombus can rarely occur in islet-cell tumors, again mimicking an
adenocarcinoma of the pancreas (Figure 29).

Another uncommon appearance of islet-cell tumors is pancreatic duct
involvement. While mild mass effect upon the pancreatic duct is commonly
seen, occasionally significant narrowing or pancreatic duct obstruction
and subsequent dilatation can be present (Fig-ure 30). Obstruction may
be so severe that intrahepatic biliary ductal dilatation may also be
present (Figure 31). In these cases, the degree of obstruction is again
usually less than would be expected with adenocarcinoma.

Once the diagnosis and staging of a pancreatic islet-cell tumor is
performed, imaging is helpful in determining the success of surgical
treatment and monitoring for signs of recurrence. Recurrence may occur
locally in the postoperative site, present as regional lymphadenopathy,
or appear as distant metastatic disease in the liver, lungs or bone
(Figure 32). Patients who are not surgical candidates are also imaged to
assess for therapy response (Figure 33).

Conclusion

The radiologist should be familiar with both typical and atypical
imaging appearances of pancreatic islet-cell tumors and the appearance
of metastatic disease to help determine whether a patient is a surgical
candidate. The classic appearance of pancreatic islet-cell tumors is a
solitary, well-circumscribed hypervascular lesion that does not disrupt
the pancreatic duct. Advanced disease may present as regional adenopathy
or distant metastases to liver, bone and/or lungs. Atypical appearances
include isodense lesions, cystic change and internal calcifications.
Rarely, islet-cell tumors may mimic a pancreatic adenocarcinoma by
narrowing or obstructing the pancreatic duct or causing vascular
encasement, occlusion or invasion.